A continuing long-range goal of the program is to examine the pathophysiology of renal disease by the use of clearance, micropuncture and biochemical techniques. Studies will be continued in an effort to clarify the functional characteristics of the chronically diseased kidney, and in particular, to define the changes in the operation of control systems which accompany the evolution of uremia. Particular interest will be devoted to the patterns of adaptation that occur in the residual nephrons as renal mass decreases with respect to the excretion of Na, PO4, and K. Studies on the control system governing the renal, excretion of Na will be extended with emphasis on an inhibitor of Na transport present in the blood of uremic patients. Studies will be continued on the pathogenesis and prevention of secondary hyperparathyroidism in chronic renal disease. Evidence in experimental animals indicates that the development of hyperparathyroidism may be prevented by dietary manipulations. These studies will be extended to include patients and long-term follow up of animals with experimental renal disease. The effects of phosphate and parathyroid hormone on glucose reabsorption and metabolism will be explored in normal and uremic animals. A new area of interest relates to the pathogenesis and functional alterations of glomerulonephritis (GN). The use of experimental models and the application of glomerular permeability measurements to the study of patients with GN is contemplated. The effect of therapeutic agents on the natural history of experimental and spontaneously occurring GN will be studied. Studies on the biochemical adaptations occurring in the diseased kidney will be continued with emphasis on the mechanisms that regulate acid excretion, gluconeogenesis and substrate oxidation. The functional patterns and mechanisms responsible for post-obstructive diuresis will be investigated using animal models. Maturation of tubular function in the fetal, neonatal and mature kidney will be studied. A seond general area of interest relates to the biology of ion transport across isolated membranes (toad bladder and frog skin).